Tetraneuron Secures Funding to Advance First-in-Class AAV Gene Therapy for Alzheimer’s disease

December 11, 2025 — Madrid-based biotech Tetraneuron has announced the successful completion of a new funding round, backed by GIMIC Ventures, to accelerate the clinical development of its groundbreaking Alzheimer’s disease treatment. The lead candidate, TET-101, is a proprietary adeno-associated virus (AAV)-based gene therapy that aims to halt disease progression by restoring neuronal homeostasis.

While the company did not disclose the exact sum of the new investment, previous similar financing rounds for the company ranged between €5–15 million. The funds will advance the AAV therapy into clinical trials across Europe.

The E2F4DN Mechanism and AAV Delivery

Tetraneuron’s platform, a spin-off from Spain’s renowned Cajal Institute, centers on E2F4DN, a dominant-negative form of the E2F4 transcription factor. E2F4 is understood to be a master regulator of numerous neuronal pathways, controlling processes from cell cycle arrest to DNA repair.

The gene therapy approach modulates E2F4 activity to prevent neurons from erroneously re-entering the cell cycle, a key driver of neurodegeneration. By intervening at this upstream molecular root, the AAV therapy is designed to reduce amyloid-beta accumulation, improve synaptic connectivity, and enhance neuroprotection.

The therapeutic effect is achieved via a single injection into the cisterna magna. The therapy utilizes AAV serotype 9, a well-established drug vector known for its ability to target the central nervous system (CNS) effectively. To maximize safety, the AAV delivery system also employs a neuron-specific promoter, hSyn1, to localize the therapeutic gene to brain tissue, mitigating the chances of off-target effects.

Advancing to European Trials

Preclinical studies of TET-101 have demonstrated a unique safety and efficacy profile. With this new financing secured, Tetraneuron is preparing to submit a Clinical Trial Application (CTA) in Europe. The company has already achieved key regulatory milestones, including a Pre-IND meeting with the U.S. FDA in 2022.

If successful, TET-101 could become the first gene therapy fully developed within Spain’s advanced therapies ecosystem to progress into clinical execution.